About 3-4% of all fractures are estimated to be open fractures, where the fracture is exposed through defects in the skin and soft tissues. This equates to about 250,000 open fractures in the United States annually. Open fractures present a high risk of infection. Infection results in considerable financial burden to both the patient an healthcare system, requires repeat operations (often more than one), and can cause delayed fracture healing or nonunion. There is no suitable option available for local antimicrobial deliver to many open fractures. A biocompatible local delivery vehicle with a fast degradation time could provide effective coverage to a much wider range of open fractures than possible with available materials. Such a technology would provide a real benefit to patients and healthcare providers alike. A promising approach for preventing infections following open fractures is to use a resorbable controlled release carrier, SB Gel, for the sustained release of antimicrobial drugs. These new gels offer the following advantages for improved prevention of infection: 1) sustained and complete antibiotic release; 2) soft yet cohesive physical structure allowing for complete coverage of wound and device surfaces, and 3) rapid degradability allowing for normal bone healing and without requiring removal. The goal of the proposed work is to identify and develop a local delivery product that provides broad-spectrum antimicrobial coverage over the entire surgical wound following an open fracture. This would significantly reduce infection rates by killing microbes prior to (and in the early stages of) biofilm formation. To do this, the release o silver nanoparticles and gentamicin will be evaluated from SB Gel. In parallel, susceptibility of bacterial biofilms in response to these drugs will be determined. The effectiveness of silver nanoparticles and gentamicin released from SB Gel in the treatment of MRSA osteomyelitis will be evaluated. Successful completion of the proposed work will provide critical data regarding the safety and effectiveness of these novel antimicrobial-loaded gels, and in particular their use to prevent infection following open fractures. Data from this work is expected to support concurrent efforts toward commercialization and lead directly to studies supporting an Investigational New Drug application to FDA's Center for Drug Evaluation and Research.